Dr. von Diezmann is a biophysicist who studies how cells regulate the pathway used to repair broken DNA. Errors in specific DNA repair pathways are an early step in the development of many cancers, such as with defects in homologous recombination for breast, ovarian, and pancreatic cancers. The Diezmann lab uses high-resolution microscopy techniques to visualize the process by which DNA breaks are designated for specific repair fates, working primarily in live meiotic nuclei of the model organism C. elegans. By elucidating the mechanisms by which protein assemblies form and transmit information along chromosomes and throughout the nucleus, her lab will help provide a foundation for the development of novel chemotherapies based on modulating the DNA damage response.

Dr. Zheng [Connie and Bob Lurie Fellow] is developing small molecules that selectively inhibit the protein K-Ras(G12D). Pancreatic ductal adenocarcinoma (PDAC) is the most lethal common cancer due to the infrequency of early diagnosis and the lack of targeted or immune therapies. A high percentage (>90%) of PDAC patients harbor KRAS mutations, with the majority expressing the K-Ras(G12D) missense mutation. Despite extensive drug discovery efforts across academia and industry, there are no approved drugs directly targeting oncogenic K-Ras(G12D). K-Ras lacks an apparent surface topology for reversible small molecule binding, leading to its notorious characterization as “undruggable.” Dr. Zheng is searching for small molecules that form a permanent bond with the mutant protein at its missense site and inhibit its interaction with effector proteins.